Seven- and thirty-day mortality in digoxin poisoning: Results from the DIGITOX study.

BACKGROUND: Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status and the presence of electrocardiographic and electrolytic disturbances. OBJECTIVE: To identify factors associated with seven-day and thirty-day mortality in digoxin poisoning. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective, observational, multicenter study was conducted across 15 Hospital Emergency Departments (HED) in Spain. All patients over 18 years of age who presented to participating HEDs from 2015 to 2021 were included. The inclusion criteria encompassed individuals meeting the criteria for digoxin poisoning, whether acute or chronic. OUTCOMES MEASURE AND ANALYSIS: To identify independent factors associated with 7-day and 30-day mortality, a multivariate analysis was conducted. This analysis included variables of clinical significance, as well as those exhibiting a trend (p < 0.1) or significance in the bivariate analysis. MAIN FINDINGS: A total of 658 cases of digoxin poisoning were identified. Mortality rates were 4.5% (30 patients) at seven days and 11.1% (73 patients) at thirty days. Regarding 7-day mortality, the mean age of deceased patients was comparable to survivors (84.7 (8.9) vs 83.9 (7.9) years; p = ns). The multivariate analysis revealed that factors independently associated with 7-day mortality encompassed the extent of dependence assessed by the Barthel Index (BI 60-89 OR 0.28; 95% CI 0.10-0.77; p = 0.014 and BI>90 OR 0.22; 95% CI 0.08-0.63; p = 0.005), the identification of ventricular arrhythmias (OR 1.34; 95% CI 1.34-25.21; p = 0.019), and the presence of circulatory (OR 2.84; 95% CI 1.19-6.27; p = 0.019) and neurological manifestations (OR 2.67; 95% CI 1.13-6.27; p = 0.025). Factors independently associated with 30-day mortality encompassed extent of dependence (BI 60-89 OR 0.37; 95% CI 0.20-0.71; p = 0.003 and BI>90 OR 0.18; 95% CI 0.09-0.39; p < 0.001) and the identification of circulatory (OR 2.13; 95% CI 1.10-4.15; p = 0.025) and neurological manifestations (OR 2.39; 95% CI 1.25-3.89; p = 0.006). CONCLUSIONS: The study identifies the degree of dependency assessed by the Barthel Index and the presence of cardiovascular and neurological symptoms as independent predictors of both 7-day and 30-day mortality. Additionally, the detection of ventricular arrhythmia is also an independent factor for 7-day mortality.

[Multidisciplinary management of voluntary pink oleander poisoning: How to estimate the quantities ingested?] / Prise en charge multidisciplinaire d'une intoxication volontaire au laurier rose : comment estimer les quantités ingérées ?

This is a case of voluntary ingestion of Nerium oleander leaves in an adolescent requiring the use of atropine and emergency chartering of antidigoxin antibodies (Digifab®) due to the difficulty of assessing oleandrin level and associated toxicity. Upon hospital admission, a digoxinemia was performed (0.44µg/mL) and the presence of oleandrine was detected. Oleandrin levels at toxic levels may be suspected by a measure of blood digoxin and explain the patient's clinical signs, which could adapt the therapeutic management.

Predictive Factors for Recurrence of Serious Arrhythmias in Patients with Acute Digoxin Poisoning.

Although digoxin poisoning has declined in the past decades, it still has deleterious outcomes. The hallmark of serious life-threatening arrhythmias remains challenging due to its non-specific initial presentation. Therefore, this study aimed to evaluate the initial predictive factors for recurrent serious arrhythmias and the need for temporary pacing in acute digoxin-poisoned patients. This retrospective cohort study included all patients with acute digoxin poisoning admitted to Tanta University Poison Control Center from 2017 to 2020. Demographic and toxicological data, poisoning severity score (PSS), laboratory investigations, and serial ECG monitoring data were documented. Patients were divided according to their age into a childhood group and adolescence & adulthood group. Each age group was divided into two subgroups according to the presence of recurrent serious arrhythmias. Patient outcomes, including intensive care unit admission, temporary pacing, and in-hospital mortality were recorded. A percentage of 37.34% (n = 31) of the included patients had recurrent serious arrhythmias in both groups. Recurrent serious arrhythmias groups had significantly low heart rate, prolonged PR interval, high PSS, Mobitz II dysrhythmias, elevated serum digoxin, serum potassium and serum creatinine, and increased adverse outcomes compared to other groups. Logistic regression analysis showed that only serum digoxin and potassium levels were significant independent predictors of recurrent serious arrhythmias and temporary pacing. Serum digoxin level had an excellent discriminatory power with the best sensitivity and specificity, followed by serum potassium level in both groups. Thus, monitoring serum digoxin and potassium levels is essential in all patients with acute digoxin poisoning, especially with limited Fab availability.

Calcium channel blocker and beta blocker overdose, and digoxin toxicity management.

While relatively uncommon, an overdose of calcium channel blockers, beta blockers, or digoxin can result in significant morbidity and mortality, and management can be complex. An acute overdose will require different management strategies than chronic toxicity while on therapeutic dosing. Toxicity from these agents must be considered in bradycardic and hypotensive patients. This supplement provides an evidence-based overview of emergency department management of calcium channel blocker overdose, beta blocker overdose, and digoxin toxicity, and focuses on the caveats of treatment for each.

Calculated decisions: DigiFab® (Digibind®) Dosing for Digoxin Poisoning.

A review of the evidence behind the DigiFab® dosing calculator, which provides dosing for digoxin immune Fab in patients with confirmed digoxin poisoning or overdose.

Digoxin-specific Fab and therapeutic plasma exchange for digitalis intoxication and renal failure.

Treatment of chronic digitalis intoxication includes suspension of drug intake, which may be sufficient in case of mild manifestations, and supportive measures. Severe bradycardia requires the administration of atropine or isoproterenol; placement of a temporary pacemaker may be required in case of absent response to pharmacological therapy. Severe and life-threatening manifestations should be treated with digoxin-specific fragment antigen binding antibodies (Fab). Therapeutic plasma exchange has been suggested, in addition to Fab therapy, to maximize the clearance of Fab-digoxin complexes in patients with renal failure. To date, few case reports have described the use of such a therapeutic approach; currently, extracorporeal methods are not recommended as part of the treatment of digitalis intoxication, and stronger evidence is required to establish their benefit.

Immediate and 30 days mortality in digoxin poisoning cases attended in the Hospital Emergency Services of Catalonia, Spain. / Mortalidad inmediata y a los 30 días en las intoxicaciones digitálicas atendidas en servicios de urgencias de Cataluña.

OBJECTIVES: Digoxin poisoning is a frequent reason for seeking emergency care. This study aimed to assess mortality related to digoxin poisoning. MATERIAL AND METHODS: Descriptive observational study of digoxin poisonings attended in the emergency departments of 4 hospitals in Catalonia from 2013 through 2015. We gathered data relevant to the poisonings and recorded immediate and 30-day mortality. Factors possibly related to mortality were explored. RESULTS: A total of 171 digoxin poisonings were attended. Seven (4.1%) were acute and 164 (95.9%) were chronic. The immediate and 30-day mortality rates were 6.4% and 13.4%, respectively. Bivariate analysis did not identify factors related to immediate mortality. However, the variables more often associated with 30-day mortality in this analysis were acute poisoning (after which 13% died vs 2.7% of those with chronic poisoning, P=.05), suicide attempts (8.7% of whom died vs 0.7%, P=.048), more compromised renal function (21.7% vs 9.5%, P=.037), fewer neurologic symptoms (4.3% vs 17.8% with more symptoms, P=.005), higher mean digoxin concentrations (4.7 mg/dL in those who died vs 3.7 mg/dL, P=.027), and a lower Barthel index (mean [SD] 49.1 [33.4] in those who died vs 70.3 [28.5]; P=.006). Logistic regression analysis identified serum digoxin concentration to be independently associated with immediate mortality. A lower Barthel index was associated with 30-day mortality. CONCLUSION: Immediate mortality is related to a high digoxin concentration in serum, and 30-day mortality to a low Barthel index.

OBJETIVO: La intoxicación digitálica es un motivo frecuente de consulta en los servicios de urgencias hospitalarios (SUH). El objetivo de este estudio es conocer la mortalidad asociada a dicha intoxicación. METODO: Estudio descriptivo y observacional de las intoxicaciones digitálicas atendidas en los SUH de 4 hospitales de Cataluña durante los años 2013-15. Se recogieron datos relativos a la intoxicación, la mortalidad inmediata y a los 30 días. Se analizó la existencia de posibles factores asociados a la mortalidad. RESULTADOS: Se registraron 171 intoxicaciones digitálicas. Siete eran agudas (4,1%) y 164 (95,9%) crónicas. La mortalidad inmediata fue del 6,4% y a los 30 días fue del 13,4%. El análisis binario no identificó ningún factor relacionado con la mortalidad inmediata. En cuanto a la mortalidad a 30 días, los pacientes que fallecieron tenían con mayor frecuencia una intoxicación aguda (13% vs 2,7%; p = 0,05), había más intoxicaciones con intencionalidad suicida (8,7% vs 0,7%; p = 0,048), más afectación renal (21,7% vs 9,5%; p = 0,037), menos sintomatología neurológica (4,3% vs 17,8%; p = 0,005), mayor digoxinemia (4,7 mg/dl vs 3,7 mg/dl; p = 0,027) y menor puntuación en el índice de Barthel (IB) (49,1 (33,4) vs 70,3 (28,5); p = 0,006). El análisis de regresión logística identificó la digoxinemia como un factor independiente de mortalidad inmediata y la puntuación en el IB en la mortalidad a 30 días. CONCLUSIONES: La digoxinemia se relaciona con la mortalidad inmediata y el IB se relaciona con la mortalidad a 30 días.

Clinical outcomes from early use of digoxin-specific antibodies versus observation in chronic digoxin poisoning (ATOM-4).

Introduction: In our previous study on chronic digoxin poisoning, there was a minor improvement after treatment with digoxin-specific antibody (digoxin-Fab). We hypothesised patients with elevated digoxin concentrations may derive little benefit from digoxin-Fab because their presenting complaint was more closely related to their multiple co-morbidities. We aimed to compare the outcome of patients who were initially treated with digoxin-Fab with those that received supportive care. Method: Patients were prospectively recruited to the study if they had an elevated digoxin concentration, signs or symptoms of toxicity thought to be from digoxin. Patients who were initially managed with digoxin-Fab were compared with those not initially receiving digoxin-Fab (observation group). Patients presented with ventricular arrhythmias before initial assessment were excluded from the analysis. Primary outcome was mortality. Secondary outcomes were length of stay (LOS), change in heart rate (HR) and potassium concentration. Results: From September 2013 to January 2018, 128 patients were recruited of which 78 (61%) received initial digoxin-Fab. Digoxin-Fab and supportive care groups had an initial median heart rate of 46 (range: 20-120) vs 52 bpm (range: 29-91) (p = .06), systolic blood pressure of 110 mmHg (range: 65-180) vs 125 mmHg (range: 90-184) (p = .009), respectively. Digoxin concentrations 4.4 nmol/L (range: 3.3-9) vs 4.2 (range: 2-11.2) (p = .42) and potassium concentrations 5.4 mmol/L (range: 3-11) vs 5.1 mmol/L (range: 3.5-8.2) (p = .33) were similar. Median dose of digoxin-Fab used was 1.5 vials (IQR: 1-2). There were 9 (12%) deaths in the Fab group compared to 7 (14%) in those treated with supportive care (risk difference -2.5%; 95% CI: -14 to 9%; p = .68). The median LOS was six days in both groups. Mean changes in potassium concentration [-0.5 ± 0.1 vs. -0.4 ± 0.1 mmol/L; difference -0.1 (95% CI: -.02, 0.4), p = .70] and HR within 4 h [8 ± 1 vs. 7 ± 3 bpm; difference -1.0 (95% CI: -6.7, 4.8), p = 0.74] were similar in the two groups. Conclusions: This study did not appear to show any benefit from the routine use of digoxin-Fab in patients thought to have chronic digoxin poisoning. These patients have multiple co-morbidities that may be contributing to their clinical features, other treatments are often equally effective.

Extracorporeal treatments in poisonings from four non-traditionally dialysed toxins (acetaminophen, digoxin, opioids and tricyclic antidepressants): A combined single-centre and national study.

The use of extracorporeal treatments (ECTRs) for poisonings with four non-traditionally dialysed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a 2-Phase retrospective analysis evaluating the main indication for ECTRs in patients with poisoning from a NTDT (defined for this study as acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed all cases from a single site (New York City Poison Control Center) between the years 2000 and 2016, and the second phase surveyed all United States Poison Control Centers (PCCs). In Phase 1, demographics, toxin ingested and main indication for ECTR were extracted. In Phase 2, a query to the National Poison Data System using the a pragmatic subset of inclusion criteria from Phase 1 restricted to single toxin ingestions over a narrower time frame (2014-2016) provided the cases for study. A structured online questionnaire was sent to all United States PCCs to request their database review regarding the indication for ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat underlying medical conditions or poisoning-related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important.

Enzalutamide and analytical interferences in digoxin assays.

Objective: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 µg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 µg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis. Methods: The second patient's digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi® (40mg) capsule. Results: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient's plasma (12,5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method. Conclusions: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.

Unusual digoxin toxicity with myocardial injury.

A 38-year-old healthy male presented with vomiting and profuse diarrhea, associated with blurry and yellow coloration of the vision (xanthopsia). Laboratory workup was unremarkable, except for hyperkalemia (K 5.2 mEq/L) and mildly elevated troponin level 0.11 ng/mL (cut-off value 0.08). An electrocardiogram showed sinus bradycardia with deep scooping of the T waves. Although the patient denied intake of any drugs, herbs, consumption of plants, a digoxin level was drawn and was significantly elevated >5ng/mL (therapeutic range 0.8-2.0). Further questioning revealed that the patient was a pharmacist mixing raw material to fabricate medication, and that he could have incidentally ingested contaminated water. His symptoms improved with parallel improvement in the electrocardiogram T wave abnormalities. An echocardiogram was normal. The positive troponin was felt to be secondary to severe digoxin toxicity. Review of the literature however showed no report of elevated troponin in the setting of digoxin toxicity.

[Digoxin poisoning: new prospects for therapy].

The filter has been approved by the Food and Drug Administration for the removal of beta-2 microglobulin in patient undergoing hemodialysis. We used the filter (the patient agrees) off label, in the course of digitalis intoxication and we have shown that the filter is capable of removing the drug effectively.